Variant 2-222201817-C-CA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BA1

The NM_181458.4(PAX3):c.1420+126_1420+127insT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 127,078 control chromosomes in the GnomAD database, including 3,188 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.24 ( 3188 hom., cov: 24)

Exomes 𝑓: 0.28 ( 438 hom. )

Failed GnomAD Quality Control

Consequence

PAX3
NM_181458.4 intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

Conservation

PhyloP100: -0.474

Variant links:

Genes affected

PAX3 (HGNC:8617): (paired box 3) This gene is a member of the paired box (PAX) family of transcription factors. Members of the PAX family typically contain a paired box domain and a paired-type homeodomain. These genes play critical roles during fetal development. Mutations in paired box gene 3 are associated with Waardenburg syndrome, craniofacial-deafness-hand syndrome, and alveolar rhabdomyosarcoma. The translocation t(2;13)(q35;q14), which represents a fusion between PAX3 and the forkhead gene, is a frequent finding in alveolar rhabdomyosarcoma. Alternative splicing results in transcripts encoding isoforms with different C-termini. [provided by RefSeq, Jul 2008]

PAX3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 2-222201817-C-CA is Benign according to our data. Variant chr2-222201817-C-CA is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 334553.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Benign=1}.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAX3	NM_181458.4 linkuse as main transcript	c.1420+126_1420+127insT		intron_variant		ENST00000392070.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAX3	ENST00000392070.7 linkuse as main transcript	c.1420+126_1420+127insT		intron_variant		1	NM_181458.4	A1	P23760-7

Frequencies

GnomAD3 genomes

AF:

0.239

AC:

30384

AN:

127024

Hom.:

3182

Cov.:

show subpopulations

Gnomad AFR

AF:

0.200

Gnomad AMI

AF:

0.199

Gnomad AMR

AF:

0.223

Gnomad ASJ

AF:

0.281

Gnomad EAS

AF:

0.310

Gnomad SAS

AF:

0.311

Gnomad FIN

AF:

0.250

Gnomad MID

AF:

0.327

Gnomad NFE

AF:

0.252

Gnomad OTH

AF:

0.228

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.275

AC:

329055

AN:

1194964

Hom.:

438

Cov.:

AF XY:

0.274

AC XY:

162486

AN XY:

593592

show subpopulations

Gnomad4 AFR exome

AF:

0.228

Gnomad4 AMR exome

AF:

0.188

Gnomad4 ASJ exome

AF:

0.278

Gnomad4 EAS exome

AF:

0.263

Gnomad4 SAS exome

AF:

0.273

Gnomad4 FIN exome

AF:

0.243

Gnomad4 NFE exome

AF:

0.282

Gnomad4 OTH exome

AF:

0.275

GnomAD4 genome

AF:

0.239

AC:

30416

AN:

127078

Hom.:

3188

Cov.:

AF XY:

0.241

AC XY:

14723

AN XY:

61016

show subpopulations

Gnomad4 AFR

AF:

0.200

Gnomad4 AMR

AF:

0.224

Gnomad4 ASJ

AF:

0.281

Gnomad4 EAS

AF:

0.310

Gnomad4 SAS

AF:

0.312

Gnomad4 FIN

AF:

0.250

Gnomad4 NFE

AF:

0.252

Gnomad4 OTH

AF:

0.228

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Craniofacial-deafness-hand syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Waardenburg syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over